Rational Design of 5-Aminolevulinic Acid Derivatives Aimed at Improving Photodynamic Therapy

ISSN: 1875-5992 (Online)
ISSN: 1871-5206 (Print)


Volume 16, 12 Issues, 2016


Download PDF Flyer




Anti-Cancer Agents in Medicinal Chemistry

Formerly: Current Medicinal Chemistry - Anti-Cancer Agents

This journal supports open access

Aims & ScopeAbstracted/Indexed in

Ranking and Category:
  • 27th of 59 in Chemistry, Medicinal

Submit Abstracts Online Submit Manuscripts Online

Editor-in-Chief:
Michelle Prudhomme
Universite Blaise Pascal - C.N.R.S
Aubiere Cedex
France


View Full Editorial Board

Subscribe Purchase Articles Order Reprints

Current: 2.722
5 - Year: 2.849

Rational Design of 5-Aminolevulinic Acid Derivatives Aimed at Improving Photodynamic Therapy



Anti-Cancer Agents in Medicinal Chemistry, 2(4): 465-475.

Author(s): Adriana Casas and Alcira Batlle.

Affiliation: Viamonte 1881 10A,1056 Buenos Aires, Argentina Fax: 54 11 4811 7447

Abstract

5-aminolevulinic acid (ALA) is the first intermediate in heme biosynthesis and is therefore a precursor of protoporphyrin IX (PpIX). PpIX is used as an endogenous photosensitizer in photodynamic therapy (PDT). Several chemical modifications have been made, both on the amino and carboxyl groups of ALA to induce higher PpIX production and photosensitisation. Esterification of ALA with aliphatic lineal and cyclic alcohols was found to reduce the amount of ALA required for photosensitization. Esterification by aliphatic alcohols with carbohydrate chains equal or lower than C4 leads to porphyrin accumulation lower than ALA, whereas equal or longer than C6 chains leads to greater synthesis of porphyrin. A branch point in the alcohol located next to the site of ester cleavage limits access of the esters to the esterase active site, resulting in lower PpIX production. ALA esters of the polyethylenglycol family can induce high levels of PpIX, with some selectivity for endothelial cells toward tumor cells. On the basis of the differential expression of some aminopeptidases in tumor vasculature when compared to normal vasculature, some ALA-pseudopeptides were synthesized. In a rational design of ALA derivatives, the transport mechanism of these aminoacids into the cell is central. Due to the similar characteristics between ALA and GABA transport, a novel approach for designing new ALA derivatives which could penetrate more easily into tumoral cells, would be to take into account the structures of the inhibitors of GABA transport.

Keywords:

aminolevulinic acid, photodynamic, pd theray, protoporphyrin.



Purchase Online Order Reprints Order Eprints Rights and Permissions




Article Details

Volume: 2
Issue Number: 4
First Page: 465
Last Page: 475
Page Count: 11
DOI: 10.2174/1568011023353903
Price: $58
Advertisement

Related Journals




Webmaster Contact: urooj@benthamscience.org Copyright © 2016 Bentham Science